The role of lysosomes in the pathogenesis of copper-induced hepatotoxicity: morphological studies.

Copper-induced hepatotoxicity was evaluated in beige and conventional mice which were injected intraperitoneally with aqueous copper chloride (8 mg per kg body weight per day). Hepatic lesions developed more quickly and were more severe in beige mice and consisted of karyomegaly, progressive accumulation of lipofuscin within hepatocytes and Kupffer cells, acute necrosis of random hepatocytes, and aggregation of leukocytes within the sinusoids. In both groups of mice the hepatic lesion had a centrilobular distribution and closely paralleled the appearance and distribution of copper within hepatocytes. Overall, beige mice had more severe copper-mediated hepatotoxicity, suggesting that normal lysosomes have protective effects for hepatocytes by sequestering copper from other cytoplasmic constituents.